HORMESIS - IMPLICATIONS FOR RISK ASSESSMENT CALORIC-INTAKE (BODY-WEIGHT) AS AN EXEMPLAR

Hormesis can he considered as a parameter which has a non-monotonic re lationship with some endpoint. Since caloric intake is such a paramete r, and the impact of this parameter on risk assessment has been fairly well characterized, it can provide clues as to how to integrate the i nformation from a hermetic parameter into risk assessments for toxican ts. Based on the work with caloric intake, one could: (a) define a bio marker for hermetic effect; (b) integrate specific information on when in the animals lifespan the parameter is active to influence paramete rs such as survival; (c) evaluate component effects of the overall her metic response; and (d) address the consequences of a non-monotonic re lationship between the hermetic parameter and end-points critical for risk assessment. These impacts on risk assessments have been character ized for chronic tests, but are also true for short-term tests. A prio rity is the characterization of the dose-response curves for hermetic parameters. This quantification will be critical in utilizing them in risk assessment. With this information, one could better quantitativel y address the changes one expects to result from the hermetic paramete r, and limit the uncertainty and variability which occurs in toxicity testing.